The present invention relates to the use of angiotensin II, or an analogue thereof, for promoting fertilization of mammalian eggs, especially human eggs. In particular, it relates to the use of angiotensin II to improve sperm motility. The invention also relates to a method of promoting in vitro fertilization.
Angiotensin II is an octapeptide, usually regarded as being produced in the blood, firstly by the action of renin, an enzyme secreted by the kidney, on angiotensinogen, resulting in the formation of the decapeptide precursor, angiotensin I, and secondly the action of a dipeptidase "angiotensin converting enzyme"; this enzyme acts on angiotensin I to form angiotensin II. Angiotensin II, in turn, undergoes hydrolysis by an aminopeptidase to yield the heptapeptide angiotensin III (angiotensin 1-7).
The hormone angiotensin II (Ang II) forms part of the renin--angiotensin system which helps to control electrolyte balance and blood pressure within the body. There are several tissues within the body upon which Ang II acts, they include the adrenal gland, uterus, liver, brain and kidney.
Amongst the several established functions of angiotensin II, it is known to be involved in vasoconstriction, which leads to hypertension. Most treatments for high blood pressure will include blockage of angiotensin function in one way or another. Ang II also stimulates the secretion of aldosterone by the adrenal cortex. Aldosterone is a potent hormone which acts primarily on the kidney to promote sodium retention and thus inter alia, heightens the hypertensive effects of angiotensin acting directly on the vasculature.
Ang II is known to act on various sites in the brain, and one of its actions in animals is the regulation of thirst and drinking.
Angiotensin also has trophic effects on the vasculature, promoting growth of the muscles in the arterial wall. It is also thought to be angiogenic, i.e. it causes vascularisation of newly developing tissue.
Most of the established effects of Ang II have been found to occur via the AT.sub.1 subtype of the Ang II receptor, which is a seven transmembrane domain receptor. This receptor has been cloned and sequenced from a variety of tissues, and has been found to be a 359 amino acid polypeptide with a predicted molecular weight of around 40 kD (Bernstein and Alexander, (1992), Endocr. Rev. 13, 381-386). Studies using photo-affinity labeling and cross linking agents have suggested molecular weights for mature receptor of approximately 65 kD and 116 kD, respectively, which may reflect glycosylation of asparagine residues within the extra-cellular domain.
From the recent development of a hybridoma cell line. see Baker, S., et al, J. Mol. Endocr. 11, 241-245, (1993), it has been found possible to produce monoclonal antibodies to the AT.sub.1 subtype of the Ang II receptor. In consequence, such receptors have been found to exist both on maturing rat and human sperm tails, and on free swimming sperm obtained by vaginal lavage from mated rats, and in human ejaculated sperm.